This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The molecular chaperone Heat Shock Protein 90 (Hsp90) is the central player in a multi-component complex that is required for the folding and activation of numerous essential proteins including nuclear receptors and cell-cycle kinases. Very little is known about 'client'substrate protein and cochaperone interactions on Hsp90 or the structural rearrangements involved in the initial stages of chaperone activity. Previous biochemical work has shown that nuclear receptors and other clients are delivered to an Hsp90:Hop (Hsp90 organizing protein) complex by the Hsp70 chaperone.